A recent study published in Nature Biotechnology describes a new technique to evaluate gene expressed at an individual synapse, the juncture at which one neuron sends messages to another neuron or cell. Known as Multiple-Annealing-and-Tailing-based Quantitative scRNA-seq in Droplets (MATQ-Drop), this new approach may grant future researchers greater insight into cellular changes associated with various neurological conditions.

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The genetic code provided by DNA is transcribed to RNA, which sends messages to the cell about protein synthesis. The transcriptome describes all the RNA produced based on the basic DNA instructions, which provides a more sensitive picture of which genes are actually expressed by an organism than the DNA code itself.

The new sequencing technique isolates synaptic material from neurites (axons and dendrites) of individual neurons, and analyzes these synaptosomes for their RNA transcriptome, which the authors of the study call the “synaptome.”

Researchers applied the MATQ-Drop assay to synaptosome samples from mice and humans and identified unique gene expression profiles associated with different cell types. They found that the genes expressed at the synapse were different from the genes expressed in the nuclei of these cells.

Synaptic gene expression seemingly affected by disease state

Because gene expression changes associated with Alzheimer’s disease (AD) had only previously been studied at the single nucleus level rather than at the level of the synapse, MATQ-Drop analysis was next performed on tissue sampled from 5XFAD mice, a strain commonly used to model AD; the inflammatory state induced by AD is thought to cause microglial cells to interfere with synaptic structure and function. The results were compared to results from wild type (non-AD) mice, though only 2 animals were included in each experimental group.

The team analyzed differentially expressed genes from several types of synapses and neuron-glia junctions represented in the tissue samples. Many of the genes identified code for functions related to myelination, immune response, complement activation, and synaptic plasticity, providing new avenues for investigating functional effects of AD at the sub-cellular level.